SCN ⁻ MFs facilitate the voltage dependence of activation and induce AMF-like behavior in WT TMEM16A . (A) Pair of macroscopic currents recorded from a cell expressing the WT TMEM16A channel. The cell was dialyzed with 0.5 µM Ca²⁺ while bathed in a solution containing Cl⁻ (black) that was later replaced with SCN⁻ (red). Scale bars are valid for both sets of traces. Discontinuous blue lines indicate zero-current levels. (B) Voltage dependence of normalized conductance calculated as described in Materials and methods using the current magnitude of recordings like those shown in A, obtained in the presence of the indicated SCN⁻ MF (0.0, n = 8; 0.25, n = 7; 0.5, n = 8; 0.75, n = 7; 1.0, n = 10). Continuous lines are fits with the logistic Eq. 2 to determine V_{0.5_app} and slope values. (C)V_{0.5_app} at 0.5 µM Ca²⁺ and different SCN⁻ MF determined for WT channels. Values were obtained from fits shown in B. Note that the V_{0.5_app} value was the same in cells bathed in TEACl- or NaCl-containing solutions. (D) Slope values at different SCN⁻ MF determined for the WT channel. Values were obtained from fits shown in B. The aquamarine value was calculated from recordings obtained in TEACl. (E) Changes in current reversal potentials induced by replacing the external Cl⁻ with the indicated SCN⁻ MF. The currents were recorded from cells expressing the WT TMEM16A. The Goldman–Hodgkin–Katz equation simulated red and blue lines with P_SCN/P_Cl = 4.87 and 5.5, respectively. (F)P_SCN/P_Cl as a function of the SCN⁻ MF. Permeability ratios were calculated using the Goldman–Hodgkin–Katz equation (Eq. 3) and the changes of reversal potential shown in E.